The overall objective of this proposal is to delineate the origin, function and functional control of M cells in Peyer's patch lymphoid follicle epithelium, especially in regard to uptake and transport of antigenic foreign macromolecules. Investigations will focus on 3 areas: (1) Origin of M cells and contiguous lymphocytes -- Our hypothesis that M cells are immature columnar cells will be tested using autoradiography to compare labeling of M cells and adjacent epithelial cells. Light microscopy will be used to determine cell migration patterns of isotopically labeled cells over lymphoid follicle domes, and electron microscopy will be used to differentiate between labeling of M cells and immediately contiguous lymphocytes. Anti-theta serum labeled with horseradish peroxidase (HRP) will be used to determine ultrastructurally whether the lymphocytes in the follicle epithelium adjacent to M cells, which can not be visualized with light microscopy, are T cells. (2) Structural components of M cells relevant to their transport function --Antibody against mouse IgA labeled horseradish peroxidase will be used to determine whether IgA is located on the surfaces and in the transport vesicles of M cells. The technique will also identify B cells relative to M cells and within Peyer's patch follicles which are committed to IgA production by labeling incorporated in their surface membranes. Because lysosomes in the mucosal barrier limit transport of luminal macromolecules, we will determine the size and distribution of lysosomes in M cells, as compared to those in adjacent columnar cells, using ultrastructural histochemical identification and morphometric analysis. (3) Control of M cell function and structure -- Endogenous and exogenous steroids terminate transport of luminal antibody and particulate material through neonatal rat ileal intestinal cells. Because M cells are structurally similar to neonatal cells, we plan to examine the effect of cortisone acetate on their uptake and transport of ferritin. We will also determine how prior oral immunization with ferritin influences ferritin uptake and transport by M cells. We will compare the effect of Giardia on M cells in normal and immune logically dificient mice.